Fabrication and Multi-antitumor Effect of Novel Dextran-hemin Crosslinked Micelles Triggered by Photo Conditions†

doi:10.7503/cjcu20141102

Abstract

Abstract:

In order to search for novel candidate drug endowed with better antitumor activities and less neurotoxicities, a novel crosslinked dextran-hemin micelle was synthesized. Hemin grafted to dextran is not only used as a phototriggered switch for the controlled release of the loaded 5-fluorouracil(5FU) quickly, but also simultaneously as a photosensitizer for photodynamic therapy(PDT) under laser irradiation. The prepared micelles exhibit high stability against extensive dilution of solution which can restrain premature drug loss and reduce side effect to human bodies. The micelles possess good biocompatibility as well. More importantly, the 5FU loaded crosslinked dextran-hemin micelles present higher antitumor effect than those of free 5FU or crosslinked micelles under laser irradiation, indicating the excellent synergetic antitumor effect of hemin with 5FU in the as-prepared micelles.

Key words: Dextran-hemin(Dex-H) crosslinked micelle, 5-fluorouracil, Singlet oxygen, Multi-antitumor effect

CLC Number:

O631

TrendMD:

LI Xianhua, ZHANG Leigang, WANG Xuexue, YU Qingbo. Fabrication and Multi-antitumor Effect of Novel Dextran-hemin Crosslinked Micelles Triggered by Photo Conditions^†[J]. Chem. J. Chinese Universities, 2015, 36(5): 1004.

Figures/Tables 9

Scheme 1 Formation schematic illustration of crosslinked Dex-H micelles and photo-triggered multimodal cancer therapy

Fig.1 UV-Vis spectra of hemin measured at different irradiation time(A) and ESR spectrum of hemin after laser irradiation(B) Time/min: a. 0; b. 5; c. 10.

Fig.2 UV-Vis(A) and FTIR(B) spectra of Dex-H(a) and dextran(b), FTIR difference spectrum(C) and FTIR spectrum of crosslinked micelles(D)

Fig.3 Size distribution of micelles before(a) and after(b) cross-linking(A) and AFM images of micelles before(B) and after(C) cross-linking

Fig.4 Change of I372/I383 of micelles before(a) and after(b) cross-link upon addition of H2O(A), AFM image(B) and dynamic light scattering(DLS)(C) of crosslinked micelles after laser irradiation(5 min) and in vitro cytotoxicity of crosslinked micelles against HeLa cells at different concentrations of polymer after 24 h incubation(D)

Fig.5 Release profiles for 5-FU loaded in crosslinked micelles under different conditions

Fig.6 UV-Vis spectra of crosslinked micelles measured(A) and singlet oxygen produced with crosslinked micelles under laser irradiation(B) t/min: a. 0; b. 6.

Fig.7 Fluorescence images of HeLa cells incubated with free 5FU(A—C), crosslinked micelles(D—F) and 5FU-loaded crosslinked micelles for 3 h(G—I)(H) and (I) are exposed to laser light source for 1 min after 1.5 h incubation. Each series can be classified to cell nucleus dyed in blue by Hoechst 33342(A, D, G), red by PI(B, E, H) and the merged images of both above(C, F, I), respectively.

Fig.8 Cell viability with free 5FU(a), crosslinked micelles(b) and 5FU-loaded crosslinked micelles under laser irradiation for 24 h incubation(c)The cell viability profiles determined by MTT.

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